Propolis Use in Dentistry: A Narrative Review of Its Preventive and Therapeutic Applications

Propolis is a resinous substance produced naturally by bees, and it consists of the exudates of plants mixed with enzymes, wax, and pollen. Propolis continues to gain considerable scientific interest due to its potential health benefits. The modern-day use of propolis in pharmaceutical preparations, such as toothpastes, mouthwashes, chewable tablets, mucoadhesive gels, and sprays, is increasing. However, the effectiveness of using propolis-containing pharmaceuticals in dentistry is not clear. The present paper aims to review the literature on the dental applications of propolis in preventive dentistry, periodontics, oral medicine, and restorative dentistry and discuss its clinical effectiveness. A literature search was conducted using Scopus, PubMed, and Web of Science databases. In total, 104 studies were included, of which 46 were laboratory studies, 5 animal studies, and 53 human clinical studies. Overall, the laboratory studies revealed a range of antimicrobial effects of propolis on oral pathogens. Clinical investigations of propolis in biofilm and dental caries control as well as adjuvant periodontal therapies reported positive outcomes in terms of plaque control, pathogenic microbial count reduction, and periodontal tissue inflammation control. Additional investigations included the use of propolis for the management of recurrent aphthous stomatitis, oral mucositis, and cavity disinfection after caries removal as well as the development of a range of restorative dental materials. Based on the reported outcomes of the studies, the clinical usage of propolis has potential. However, the majority of the evidence is derived from studies with flaws in their methodological design, making their results and conclusions questionable. As a consequence, properly designed and well-reported clinical studies are required to affirm the effectiveness of propolis for dental applications. Additionally, the safety of propolis and the optimal concentrations and extraction methods for its clinical use warrant further investigation. Utilisation of standardised propolis extracts will help in quality control of propolis-based products and lead to the achievement of reproducible outcomes in research studies.


Introduction
Propolis is a resinous substance produced naturally by bees, and it consists of the exudates of plants mixed with enzymes, wax, and pollen.The term "propolis" is Greek in origin (from pro "in defense" and polis "the city") and, in the context of bees, means "defense of the hive."As the term suggests, propolis is used by bees for hive protection against bacteria, viruses, fungi, and parasites. 14][5] These characteristics vary not only as a consequence of variations in the botanical sources of the constituents but also as a result of changes in the environmental conditions, making standardisation and quality control challenging.Although a range of constituents have been reported, crude propolis is generally composed of 50% plant resin and balsam, 30% beeswax, 10% essential and aromatic oils, 5% pollen, and 5% organic and inorganic compounds. 6The predominant chemical compounds of propolis are flavonoids, phenols (e.g.phenolic glycerides, phenolic acids and their esters, lignans, and stilbenes), terpenes, and terpenoids, with variable amounts of fatty acids, alcohols, alkaloids, sugar, amino acids, vitamins (e.g.B 1 , B 2 , B 3 , B 5 , B 6 , C, and E), and minerals (e.g.calcium, iron, potassium, magnesium, sodium, aluminium, boron, barium, chromium, manganese, nickel, strontium, and zinc). 1 Propolis has a characteristic smell, and its colour varies from yellow to green and red to dark brown depending on the plant source and the collection season. 7he composition and biological properties of propolis are affected by the solvents and techniques used for its extraction.Ethanol, water, and propylene glycol have been used as solvents, and the selection of the most appropriate chemical depends on the intended use of propolis. 8In addition to the use of solvents, several propolis extraction techniques are used, including maceration and ultrasound-assisted, microwave-assisted, and supercritical carbon dioxide extraction. 1 Amongst these techniques, ultrasound-assisted propolis extraction has been reported to be the optimal method in terms of extraction time and yield. 9The main source of commercial propolis is the honeybee, Apis mellifera, with less common types of propolis produced by stingless bee species, such as Trigona sirindhornae. 2he reported therapeutic and health-promoting effects of propolis include antibacterial, 10,11 antiviral, 12 antifungal, 13 anti-inflammatory, 14 antitumour, 15 wound healing, 16 and immunomodulation. 17The mechanism of action of propolis, although not well studied, has been described in the literature through its potential to activate the host natural defense and to impair the mobility, adherence, and metabolisms of microorganisms. 10For centuries, propolis was recognised as a therapeutic agent by several ancient cultures including the Egyptians and Greeks. 18However, its modern-day use in pharmaceutical preparations is increasing as its health benefits become more evident. 2Propolis-containing oral capsules, chewable tablets, lozenges, drops, sprays, creams, ointments, mucoadhesive gels, oral syrups, toothpastes, and mouthwashes are commercially available products, yet their clinical effectiveness is not clear.
In the medical field, the effectiveness of propolis has been investigated with variable success for the management of various infections and diseases, such as diabetic foot ulcers, 19,20 skin wounds, 21 cutaneous warts, 22 respiratory tract infections, [23][24][25] vaginal infections, 26 muscle fatigue, 27 and hypertension. 28Propolis use in the management of postoperative inflammation after excisional hemorrhoidectomy, [29][30][31] inflammation and infection in patients undergoing hemodialysis, [32][33][34] and inflammation in people with HIV infection has also been reported. 35urthermore, there is growing interest within the dental field in the use of natural medicinal products with inherent antimicrobial activity, such as propolis, as alternative antimicrobials since antimicrobial resistance within individuals has become a serious global health threat. 36The antimicrobial efficacy of propolis against oral pathogenic microorganisms has been extensively assessed, with an overall strong efficacy reported. 37- 40Propolis not only represents a promising alternative antimicrobial agent but also has a range of favourable biological activities, 41 making its use in preventing or treating various dental and oral conditions highly attractive.This narrative review aims to provide an overview on the applications of propolis in the fields of preventive dentistry, periodontics, oral medicine, and restorative dentistry, highlighting its clinical effectiveness and identifying research gaps that need to be addressed.

Methods
An electronic literature search was conducted using Scopus, PubMed, and Web of Science databases up to and including September 2023.A combination of key words, including "propolis," "bee glue," "flavonoids," "dental," and "antimicrobial" were used in the databases following their syntax rules.All combinations using (AND, OR) were utilised to refine the search results.Primary studies focussed on propolis applications in preventive dentistry, periodontics, oral medicine, and restorative dentistry were included.Laboratory, animal, and human clinical studies were all included to provide a general comprehensive overview of evidence on the topic.No time restrictions were applied and only English records were included.Reviews, editorials, and conference proceedings were excluded.An additional manual search was carried out through reference mining of the identified studies.
All records were initially screened for relevance by 2 independent authors (MA and FA).Full texts of relevant papers were then retrieved and reviewed by 2 independent authors (HA and MME).Relevant data were extracted from the included studies and summarised in a narrative format and tables.

Results and discussion
The electronic databases searche identified a total of 351 records, of which 100 duplicate records were removed and 166 records were excluded following initial title and abstract screening due to the lack of relevance to the scope of the present review.An additional 19 records were manually detected in the reference list of the included studies.In total, 104 studies were included in this review, of which 46 were laboratory studies, 5 were animal studies, and 53 were human clinical studies.Overall, the studies investigated the effectiveness of propolis usage in biofilm control, dental caries prevention, adjuvant periodontal therapy, the management of recurrent aphthous stomatitis, chemotherapy-and radiotherapy-induced oral mucositis, halitosis, denture stomatitis, cavity disinfection after carious tissue removal, and optimisation of the properties of restorative dental materials.The usage of propolis in various dental applications and delivery formulations (vehicles) is discussed below and summarised in the Figure.

Preventive dental applications
The effectiveness of propolis usage in preventive dentistry as an agent for biofilm control and dental caries prevention has been evaluated in laboratory, animal, and human clinical studies.A summary of the studies is discussed below, with further details of the human clinical studies, in terms of design, participants, groups, and reported outcomes, presented in Table 1.

Laboratory studies
[40] Koo et al 45 reported inhibition of microbial cell attachment and water-insoluble glucan formation by glucosyltransferases in cultures of C albicans, S aureus, E faecalis, P gingivalis, and Streptococcus species after exposure to variable concentrations of the ethanolic extract of Brazil propolis.The same group evaluated in vitro the antibiofilm effects of distinct chemical components found in Brazil propolis on various species of Streptococcus and reported apigenin and tt-farnesol as the most effective inhibitors of glucosyltransferases activity and microbial growth, respectively. 51,64Similar results were reported by others, revealing the antiadhesion effect of propolis on S mutans with inhibition of glucosyltransferases expression. 49,50urthermore, several studies reported that the exact degree of propolis antimicrobial and antibiofilm efficacy is dependent on various factors, including source of origin, concentration, extraction solvent, length of exposure to the microorganisms, and type of microbial strain. 42,46,50,53,54,60oru et al 56   of Gram-positive bacteria requiring lower concentrations compared to Gram-negative bacteria.Similar results have been reported by other research groups. 47,48,57Furthermore, several studies demonstrated variation on the microbial inhibitory concentrations of propolis extracted using different solvents, including ethanol, water, ether, acetone, methyl chloride, and benzene, suggesting a clear effect of the solvent on the antimicrobial activity of propolis. 58,65imal studies Several animal studies investigated the effectiveness of propolis extracted using different solvents, including ethanol and hexane, as well as the effectiveness of propolis fractions, including apigenin and tt-farnesol, in reducing the incidence of dental caries in rats. 61,62,64,66The experimental model used in the studies involved Wistar rats infected with Streptococcus sobrinus and fed a cariogenic diet.Ikeno et al 61 reported an approximate 60% reduction of fissure caries in rats exposed to ethanolic extracts of China propolis (1 mg/mL) for 48 days.However, the authors did not report the frequency of propolis extract administration.Koo et al 64 treated rats' teeth topically twice daily for 5 weeks with various materials, including (1) apigenin (0.035%, Extrasynthese), ( 2) tt-farnesol (0.028%, Sigma Aldrich), (3) a combination of apigenin and tt-farnesol, (4) sodium fluoride (0.05%), and (5) chlorhexidine gluconate (CHX, 0.12%).The authors reported reduction of dental caries incidence in rats exposed to a combination of apigenin and tt-farnesol, sodium fluoride, or CHX by 60%, 70%, and 72%, respectively, with no statistically significant differences amongst the 3 groups. 64Furthermore, Hayacibara et al 62 and Arslan et al 66 reported equal effectiveness of ethanolic and hexane extracts of Brazil propolis in dental caries reduction in rats after twice-daily topical application for 5 weeks.

Human clinical studies
4][85][86] A summary of the key findings is presented below.

Propolis-containing mouthwash
The clinical effectiveness of propolis-containing mouthwashes in biofilm control was evaluated in several studies.In a preliminary RCT conducted by Koo et al, 67 the use of a mouthwash containing 3% Brazil propolis extract for 1 minute twice daily for 3 days, as a solo oral hygiene measure, resulted in a statistically significant reduction in plaque deposits and insoluble polysaccharides content of the biofilm amongst healthy adult participants.However, as blinding of the outcome's assessor was not reported, the study possesses a risk of bias.In another observational clinical study, by Pereira et al, 84 a statistically significant reduction in plaque deposits was reported amongst adult participants with inadequate oral hygiene who used a mouthwash containing 5% Brazil propolis extract for 1 minute twice daily after toothbrushing for up to 3 months.However, the utilised study design has a risk of bias arising from lack of control over covariates and lack of randomisation.Furthermore, although Duailibe et al 72 reported a reduction in S mutans colony counts in saliva samples of around half of participants after 7 days of thrice-daily rinsing with a mouthwash containing propolis extract, their study was not controlled.Methodical flaws were also noted in the study of Bapat et al, 69 who reported comparable effectiveness of 0.2% CHX and a mouthwash containing 0.1% propolis from India in reducing S mutans and L acidophilus colony counts in the saliva of participants after twice-daily use for up to 3 months.

Propolis-containing toothpaste
The benefit of using propolis-containing toothpaste has been assessed in several studies.In a clinical study by Mohsin et al, 85 a statistically significant reduction in S mutans colony counts in dental plaque and saliva samples of children was reported after using commercially available toothpaste containing propolis from South Korea (Probee, Seoul Propolis Co.) once daily for 4 weeks.However, the study was not controlled and the results are likely to be biased.A recent doubleblinded RCT by Lotif et al 74 reported a statistically significant reduction in plaque deposits and Lactobacillus species count in saliva amongst adolescents with fixed orthodontic appliances and inadequate plaque control after twice-daily use of a toothpaste containing 1% propolis extract from Brazil for 28 days.

Propolis-containing chewing gum and chewable tablets
Propolis-containing chewable gum and tablets have also been evaluated in several clinical studies, with variable reported outcomes.Tulsani et al 82 reported a statistically significant reduction in S mutans colony counts in children's saliva after using chewing gum containing 6.4% propolis from France for 15 and 60 minutes.This is in agreement with El-Allaky et al, 79 who reported a clear reduction in plaque deposits and biofilm microbial colony counts amongst children with high caries risk after using chewing gum containing 2% propolis from Egypt twice daily for 2 weeks.Although Martins et al 70 reported that propolis did not enhance the properties of xylitol-containing chewable tablets, Siqueira et al 81 demonstrated a statistically significant reduction in S mutans and Gram-negative bacteria colony counts in saliva samples of participants exposed to propolis and xylitol chewable tablets.This could be due to variations in the concentrations of active agents or frequencies of tablet consumption.Either way, further studies are needed, as all studies mentioned above have methodological design limitations and risk of bias.

Propolis-containing dental varnish
The effectiveness of propolis-containing dental varnish in children with high caries risk was evaluated and compared to 5% fluoride varnish.Neto et al 83 reported a significant reduction of S mutans colony counts in saliva samples of 3-to 5year-old children following application of dental varnish t h e u s e o f p r o p o l i s i n d e n t i s t r y containing as low as 1% propolis extract.Furthermore, Neto et al 87 reported that 2.5% propolis varnish was as effective as 5% sodium fluoride varnish in reducing S mutans colony counts in participants' saliva.In summary, human clinical studies reported promising outcomes in terms of propolis usage as an agent for biofilm control.However, most of the studies have methodological flaws and bias arising from inadequate information on the randomisation process, lack of controls, lack of blinding, or missing or selective reporting of the outcome data, making clear conclusions impossible to draw.Therefore, further properly designed and well-reported clinical studies are required to confirm the caries-preventive effects of propolis.Additionally, further investigations are needed to reveal any side effects associated with the clinical applications of propolis and to determine its optimal concentration and extraction method.The utilisation of standardised propolis extract is essential to help in quality control of the products and achievement of reproducible outcomes.

Periodontal applications
Propolis utilisation as an agent for adjuvant periodontal therapy has attracted scientific interest, with several laboratory and human clinical studies investigating its effectiveness in reducing pathogenic microbial counts, controlling tissue inflammation, and improving the overall health of periodontal tissues.A summary of the studies is provided below, with further details of the human clinical studies in terms of design, participants, groups, and reported outcomes presented in Table 2.

Laboratory studies
The effects of propolis extracts on various periodontal pathogens was assessed in vitro 52,54,59,62 and compared to wellestablished antimicrobials, including amoxicillin, 46 and CHX. 37,39It has been reported that both Brazil red propolis and amoxicillin exhibited similar reductions in colony counts and metabolic activity of multiple microorganisms associated with periodontal diseases after 24 hours of exposure. 55However, it is not clear whether the antimicrobial effectiveness of propolis will continue to be comparable to that of amoxicillin after shorter exposure times.Furthermore, although propolis extracts from Turkey and Brazil were reported to be as effective as CHX on biofilms of streptococci and fungi, CHX was more effective against biofilms of A actinomycetemcomitans, S aureus, and E faecalis. 37,39man clinical studies

Propolis-containing mouthwash
The addition of propolis, as a natural active agent, to mouthwashes has been assessed in human clinical studies.Kiani et al 88 reported a statistically significant reduction in gingival sulcus bleeding amongst adult patients with gingivitis, who were otherwise healthy, after twice-daily use of propolis mouthwash for 2 weeks, with the conventional tooth-brushing and dental flossing.However, it is not clear whether this result was because of propolis mouthwash usage or merely adherence to regular tooth-brushing and dental-flossing regimens amongst the participants.Lisbona-Gonz alez et al 89 and Samad et al 77 reported positive outcomes of propolis mouthwash usage in patients with periodontitis and deep periodontal pockets.However, both studies are likely to be biased due to inadequate control over covariates.

Propolis-containing toothpaste
The addition of propolis to toothpastes has been assessed in several human clinical studies.In a randomised controlled trial by Machorowska-Pieni ą _ zek et al, 90 adolescents with cleft lip and/or palate, gingivitis, and orthodontic appliances were exposed to propolis toothpaste thrice daily for 35 days.Although the authors reported reduction of plaque deposits and gingival sulcus bleeding, such findings could occur due to adherence to conventional oral hygiene practice and not because of any additional therapeutic effect.Hassan and Ahmed 86 reported reduction of gingival sulcus bleeding and inflammatory interleukin levels in the saliva of patients with gingivitis who used propolis toothpaste twice daily for 7 days.This is in agreement with the results reported by Peycheva et al, 80 who reported reduction of gingival sulcus bleeding along with eradication of multiple periodontal pathogens following the use of toothpaste supplemented with drops of propolis extract twice daily for 1 and 4 weeks.However, the results of the previously mentioned studies, together with those of other similar studies, 73,75 are likely to be biased due to inadequate control over the covariates.

Propolis-containing oral capsules
The production of oral capsules (to be swallowed) incorporated with propolis as an adjunct to periodontal therapy has been reported on a limited basis.In a multicentre RCT by Park et al, 91 adult patients with gingivitis or incipient periodontitis were subjected to daily intake of a single oral capsule containing 194 mg mangosteen and propolis for 4 and 8 weeks, in addition to conventional oral hygiene practice.Although the authors reported no significant differences between the test and control groups in terms of plaque deposit reduction, bleeding on probing, periodontal pocket depth improvement, and change in inflammatory markers, the study had selection bias, as outcomes from patients with gingivitis cannot be compared to those from patients with periodontitis and deep pockets. 91El-Sharkawy et al 92 reported absence of a clear effect of propolis oral capsules (400 mg) as adjuvants to scaling and root planing in patients with moderate to severe chronic periodontitis and type 2 diabetes mellitus.

Propolis-containing ointment and gel
Similar to the above reported findings, the production of ointments and gels with incorporated propolis as an adjunct to periodontal therapy to reduce plaque deposits has been explored.In a preliminary RCT by Nakao et al, 93 adult patients with moderate to severe chronic periodontitis were exposed to professional application of propolis ointment (10 mg/mL) in the periodontal pockets thrice monthly after the initial periodontal therapy.Although the authors reported improvement of periodontal pocket depths and clinical attachment levels with reduction of P gingivalis colonies in the gingival   76 Not clearly reported 30 participants with chronic periodontitis and presenting ≥3 nonadjacent teeth with deep pockets 25−55 20% propolis hydroalcoholic mouthwash after scaling and root planing (15)   Scaling and root planing alone (15)   India propolis extracted using ethanol (20%) PD, BOP, and PPD were recorded followed by subgingival plaque sampling at baseline and after 4 and 12 wk.
A statistically significant improvement in PD, BOP, and PPD was seen in the study group.
(continued on next page) crevicular fluid at 3 months, 93 there is a risk of bias arising from lack of information about standardisation of oral hygiene practices amongst the participants over the study period.Giammarinaro et al 94 reported equal effectiveness of topically applied propolis gel and CHX gel, in terms of resolution of gingival sulcus bleeding and improvement of periodontal pocket depths, in adult patients with chronic periodontitis who completed the initial periodontal therapy.However, the study has design limitations, and all recruited participants had gingivitis only with no pathologic periodontal pockets.Inadequate control over the covariates was also noted in the other studies reporting positive results in association with propolis ointments and gels as an adjunct to periodontal therapy. 95,96opolis-containing irrigation solution The use of propolis as an active agent in periodontal irrigation solutions has also been assessed.Pundir et al 76 and Coutinho et al 124 reported reductions in periodontal pocket depths and bleeding on probing following the use of propolis as a subgingival irrigation solution in patients with chronic periodontitis.However, Seth et al 97 reported that 0.2% CHX was superior to 25% propolis extract as a subgingival irrigation solution after scaling and root planing in patients with chronic periodontitis and deep pockets.In summary, although the clinical studies discussed here reported positive outcomes for propolis products used as adjuncts to periodontal therapy, valid scientific conclusions cannot be drawn due to methodological flaws in the reported studies.Therefore, further clinical studies that are properly designed and well conducted, with comprehensive and unbiased reporting of outcomes, are needed.

Human clinical studies
Propolis use as a remedial therapeutic agent in idiopathic RAS, in otherwise healthy individuals, has attracted scientific interest owing to its anti-inflammatory, antioxidant, immunomodulatory, and wound-healing properties.Several propolis-based products have been tested clinically in humans, including mouthwash, 98 solutions for topical application, 99 spray, 100,101 mucoadhesive film, 102 paste, 103 and oral capsules. 104The human clinical studies are discussed below, with further details, in terms of design, participants, groups, and reported outcomes, presented in Table 3.
The effectiveness of propolis mouthwashes amongst adult patients with minor RAS was assessed in one RCT, with promising results reported in terms of time until ulcer healing and pain control. 98Furthermore, improved healing was reported amongst adult patients with RAS following topical application of propolis-based solution 3 times a day. 99Accelerated ulcer epithelisation with reduction of ulcer dimension and pain intensity was also reported following usage of propolis spray 3 times a day amongst adult patients with minor RAS. 101  results were reported in another study, demonstrating pain resolution and ulcer healing following 2 and 7 days, respectively, of propolis spray usage thrice daily in comparison to 4 days for pain resolution and 9 days for ulcer healing in the control group. 100However, the latter study reported an association between silver nitrate cauterisation and better symptom resolution in RAS cases.Further studies are needed to better understand the therapeutic potential of propolis in comparison to traditional agents for the management of RAS.
In addition to the above, the inclusion of propolis extract in mucoadhesive films was evaluated in preliminary clinical study involving 24 adult patients with RAS.The authors reported effective reduction of ulcer dimension, time until healing, and pain intensity following the usage of propolisbased mucoadhesive film twice daily. 102It was suggested that this delivery vehicle could be superior to other investigated vehicles due to the sustained release of propolis and targeted delivery with anti-infective barrier formation between the ulcer and the oral cavity.However, evidence supporting this hypothesis is missing.
In summary, promising clinical results have been reported in the literature regarding propolis usage to accelerate healing and improve quality of life amongst patients with RAS who are otherwise healthy.However, further studies are needed to address several methodological flaws in the reported studies, such as lack of blinding and control over covariates.

Human clinical studies
The medicinal properties of propolis make it an attractive agent for the management of chemotherapy-and radiotherapy-induced oral mucositis. 105Several formulations and delivery vehicles have been investigated, including propoliscontaining mouthwash, [106][107][108][109][110] mucoadhesive gel, 111 paste, 112 and oral tablets. 113A summary of the studies is given below, with further details, in terms of design, participants, groups, and reported outcomes, presented in Table 4.
The effect of propolis mouthwash on the severity of oral mucositis amongst adult patients undergoing radiotherapy and chemotherapy for head and neck cancers has been assessed, with variable outcomes.Hamzah et al 106 and Akhavankarbassi et al 108 reported reductions in oral mucositis severity scores (assessed using the World Health Organization [WHO] scale) and improvement of participants' ability to eat and drink following the use of propolis mouthwash thrice daily for up to 6 weeks starting from the date of therapy initiation. 106,108On the contrary, Marucci et al 107 concluded that there was no effect of mouthwashes containing propolis, aloe vera, calendula, and chamomile on the severity of chemotherapy-induced oral mucositis following its use 4 times daily for 5 weeks.A potential explanation of the variation in the outcomes amongst the studies could be variations in cancer therapy protocol, the demographics of the participants, and the oral mucositis assessment scales used.Furthermore, Placebo mouthwash 30% Propolis (Soren Tektoos) The severity of OM was evaluated using the WHO scale at baseline and after 3 and 7 d.
- outcome variation amongst the studies could also be due to differences in propolis concentrations, origin, and extraction methods.
In addition, variable outcomes were reported following the usage of propolis-containing mucoadhesive gels, paste, and oral tablets (to be swallowed) amongst adult and children undergoing chemotherapy and radiotherapy for various types of cancers.Noronha et al 111 reported no incidence of severe oral mucositis (based on the WHO scale) following the use of propolis mucoadhesive gel thrice daily starting 1 day before radiotherapy amongst adults with head and neck cancer.Similarly, Piredda et al 113 demonstrated the reduction in the incidence of severe oral mucositis (based on the National Cancer Institute Scale) following the use of propolis oral tablets and sodium bicarbonate mouthwashes amongst female patients undergoing chemotherapy for breast cancer.In contrast, Toma zevi c and Jazbec 112 reported no effect on oral mucositis severity (based on the modified Eilers oral assessment scale) following the use of propolis paste amongst children undergoing chemotherapy for unspecified types of cancer.
In summary, although researchers have uncovered positive results, suggesting the potential benefit of propolis in the management of chemotherapy-and radiotherapy-induced oral mucositis, further studies are needed utilising controlled designs, standardised assessment methods, and standardised propolis extracts in order to arrive at sound scientific conclusions.

Miscellaneous oral medicine applications
Propolis usage has also been tested clinically for the management of denture stomatitis and morning halitosis.Improvement in denture stomatitis with reduction of Candida yeast was reported amongst a small sample of full denture wearers following twice-daily rinses with propolis-containing mouthwash for 2 weeks. 13Furthermore, a study reported a statistically significant reduction in the count of volatile sulfur compound−producing microorganisms amongst healthy adults with morning halitosis, following twice-daily rinsing with propolis-containing mouthwash for 5 days. 114Although promising clinical results were published in both studies, they were preliminary in nature and had inadequate control over several confounding factors.Therefore, further studies are needed to confirm the results.

Laboratory studies
Propolis has attracted attention because of its potential benefits when incorporated into dental materials and used for cavity disinfection during dental caries removal.6][117][118] Furthermore, addition of propolis to glass ionomer cement in order to enhance its biological properties has

Human clinical studies
Propolis use as a cavity disinfection agent following dental caries excavation has been investigated clinically on a limited basis. 121In an RCT by Prabhakar et al, 122 reduction of microbial colony counts was reported following propolis applications for 1 minute after manual caries excavation in primary molars as part of the atraumatic restorative technique.However, due to the limited number of clinical studies, further research is needed to confirm the results.

Limitations, concluding remarks, and future perspectives
The authors acknowledge the limitations of the current review, which are mainly associated with the relatively poor quality of the included studies.The majority of the included studies had methodological flaws and bias arising from either inadequate information on the randomisation process, lack of control over confounding factors, lack of blinding, and missing or selective reporting of the outcome data, making their conclusions questionable.Furthermore, the methodological variations amongst clinical studies make comparisons impossible.A strength of the study lies in the fact that the authors ensured that all data screening and extraction were performed by 2 independent and calibrated authors to ensure the quality and accuracy of the extracted data.To gain an overall view of propolis usage within the dental field, a narrative study design was adopted.In summary, various propolis-based products are available to clinicians and the general public as over-the-counter medications.Although the available literature demonstrates overall promising clinical outcomes when propolis is used, future researchers are encouraged to standardise methodological designs, propolis extraction methods, and assessment methods in order for their results and conclusions to be valid and to be compared.Furthermore, to streamline commercial production, clear guidelines for quality control and assurance of this natural product should be developed.Studies of the individual constituents of propolis will help to better understand its mechanism of action and aid the process of quality control and standardisation.
Fig -Schematic illustration of the investigated applications of propolis in preventive dentistry, periodontics, oral medicine, and restorative dentistry.A, Biofilm control and dental caries prevention; B, adjuvant periodontal therapy; C, Recurrent aphthous stomatitis; D, Chemotherapy-and radiotherapy-induced oral mucositis; E, Cavity disinfection after carious tissue removal

Table 1 -
Human clinical studies on the effectiveness of propolis usage in biofilm and dental caries control.

Table 2 -
Human clinical studies on the effectiveness of propolis usage in adjuvant periodontal therapy.

Table 3 -
Human clinical studies on the effectiveness of propolis usage in recurrent aphthous stomatitis.

Table 4 -
Human clinical studies on the therapeutic effectiveness of propolis in chemotherapy and radiotherapy-induced oral mucositis.

Table 4 .
120ntinued), chlorhexidine; CTCAE, Common Terminology Criteria for Adverse Events; OM, oral mucositis; NCI-CTC, National Cancer Institute Common Toxicity Criteria; WHO, World Health Organization; d, day; h, hour; min, minute; mo, month; wk, week; y, year t h e u s e o f p r o p o l i s i n d e n t i s t r y been attempted, with variable success.Abdallah et al119demonstrated, in a laboratory study, no impact on the colour stability and microhardness of ceramic-reinforced glass ionomer cement following the addition of 50% ethanolic extract of Egyptian propolis.On the contrary, Panahandeh et al120concluded that addition of 25% and 50% aqueous extract of Iranian propolis to resin-modified glass ionomer cement reduced the flexural and shear bond strength of the material with no apparent in vitro antimicrobial activity against S mutans. CHX